The enormous variety of biochemical reactions that comprise life are nearly all mediated by a series of biological catalysts known as enzymes. Enzymes are proteins which possess specific catalytic activities that enable them to catalyze a series of reactions, hence enabling metabolic pathways to degrade and to reconstruct products needed to maintain organisms. By the binding of substrates through geometrically and physically complementary reactions, enzymes are stereospecific in binding substrates as well as in catalyzing reactions. The stringency for this stereospecificity varies as some enzymes are more specific to the identity of their substrates, while others are capable of binding multiple substrates and can catalyze numerous types of reactions.
Examples of enzymes include, for example, guanylate kinases, phophatidylinositol 4-phosphate 5-kinases, kinases, transferases, aminopeptidases, adenylate cyclases, calpain proteases, oxidoreductases, neprilysin proteases, AMP binding enzymes and lysyl oxidases. Such enzymes have the ability to, for example: (1) modulate ATP-dependent phosphorylation of GMP, dGMP, or cGMP; (2) catalyze the formation of phosphoinositol-4,5-bisphosphate via the phosphorylation of phosphatidylinositol-4-phosphate; (3) mediate the phosphoinositide signaling cascade; (4) convert a substrate or target molecule to a product (e.g., transfer of a phosphate group to a substrate or target molecule, or conversion of ATP to ADP); (5) interact with and/or phosphate transfer to a second protein; (6) modulate intra- or intercellular signaling and/or gene transcription (e.g., either directly or indirectly); (7) modulate the phosphorylation state of target molecules (e.g., a kinase or a phosphatase molecule) or the phosphorylation state of one or more proteins involved in cellular growth, metabolism, or differentiation, e.g., cardiac, epithelial, or neuronal cell growth or differentiation; (8) convert a substrate or target molecule to a product (e.g., transfer of a methyl group to or from the substrate or target molecule); (9) interact with and/or methyl transfer to a second target molecule e.g., a nucleic acid molecule (e.g., DNA or RNA), a small organic molecule (e.g., a hormone, neurotransmitter or a coenzyme) or a protein; (10) cleave a protein precursor to maturation; (11) catalyze protein degradation; (12) catalyze the formation of a covalent bond within or between an amino acid residue (e.g., a serine or threonine residue) and a phosphate moiety; (13) modulate the cAMP signal transduction pathway; (14) modulate a target cell's cAMP concentration; (15) modulate cAMP-dependent protein kinase activity, such as protein kinase A; (16) modulate a calpain protease response; (17) modulate metabolism and catabolism of biochemical molecules, e.g., molecules necessary for energy production or storage; (18) modulate betaine synthesis from choline; (19) modulate methionine synthesis from homocysteine; (20) modulate the activity of a bioactive peptide, (21) cleave a neprilysin substrate, e.g., enkephalin; (22) modulate membrane excitability, (23) influence the resting potential of membranes; (24) modulate acetyl-CoA ligase activity; (25) promote activation of acetate; (26) promote acetate utilization; (27) enhance uptake of acetate into fatty acids and biochemical products made from fatty acids (e.g., lipids and hormones such as sterol hormones); (28) crosslink an extracellular matrix component; (29) regulate bone resorption and/or metabolism; and (30) regulate copper metabolism. Accordingly, there exists a need to identify additional human enzymes, for example, for use as disease markers and as targets for identifying various therapeutic modulators.